PXD058762-1

PXD058762 is an original dataset announced via ProteomeXchange.

Title	MDM2-amplified esophageal adenocarcinomas exhibit an activated metabolic and immunosuppressive phenotype with multiple potential therapeutic targets
Description	A complete response following neoadjuvant therapy occurs only in a fraction of patients with esophageal adenocarcinoma (EAC). Further targeted treatment options are needed to improve treatment response and patient survival. Mouse double minute 2 homolog (MDM2) is a known oncogene. Its upregulation results in a more aggressive cancer phenotype. It is currently under investigation as a potential therapeutic target. However, initial findings have not been groundbreaking. Therefore, this study aimed to identify further potential therapeutic targets in the subtype of MDM2-amplified EAC. Methods: We screened 656 patients with operable esophageal adenocarcinoma for their MDM2-amplification status using Fluorescence in situ Hybridization (FISH). 57 tumors (8.7%) were MDM2-amplified. The proteome of 35 MDM2-amplified and 37 non-amplified tumors was analyzed using mass spectrometry. 22.2% of the included patients were primarily resected, and 77.8% were neoadjuvant treated. Results: The comparison of MDM2-amplified and non-amplified tumors revealed various differently expressed proteins and pathways. Hornerin, Bystin, and subtypes of keratins (KRT1, KRT2, KRT9, KRT10) were significantly downregulated. Whereas Choline transporter-like protein 2 (CTL2), Cullin-associated NEDD8-dissociated protein 1 (CAND1), FAD- and RhoGTPase-binding protein 1 (FARP1), and Contactin 1 were upregulated in MDM2-amplified EAC. Enrichment analyses revealed that MDM2-amplified esophageal adenocarcinomas showed a more pronounced immunosuppressive phenotype due to the downregulation of interferon signaling pathways and antigen presentation. Furthermore, distinct metabolic pathways like carbon, propanoate, tryptophan, and tyrosine metabolism were upregulated in MDM2-amplified tumors. Conclusion: In this study, we investigated the whole proteome of MDM2-amplified compared to non-amplified esophageal adenocarcinomas. We described numerous potential future therapeutic targets, suggesting patients with MDM2-amplified tumors could potentially benefit from, exemplary, Mitogen-activated protein kinase kinase (MEK) inhibitors or tryptophan metabolism inhibitors. Future mechanistic studies are needed to validate these findings.
HostingRepository	PRIDE
AnnounceDate	2025-12-15
AnnouncementXML	Submission_2025-12-14_19:53:34.129.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Proteomics Facility
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-11 01:53:53	ID requested
⏵ 1	2025-12-14 19:53:35	announced

10.1186/s12885-025-15367-3;

Knipper K, Bruns CJ, Popp FC, Schmidt T, Grothey B, Quaas A, Lyu SI, MDM2-amplified esophageal adenocarcinomas exhibit an activated metabolic and immunosuppressive phenotype with multiple potential therapeutic targets. BMC Cancer, 25(1):1863(2025) [pubmed]

submitter keyword: Esophageal adenocarcinomas, Tumor microenvironment, MET signaling pathway,Oncology, Proteomics

Alexander Quaas
contact affiliation	Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany
contact email	Alexander.quaas@uk-koeln.de
lab head
Proteomics Facility
contact affiliation	CECAD Research Center
contact email	proteomics-facility@uni-koeln.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058762
     1. Label: PRIDE project
     2. Name: MDM2-amplified esophageal adenocarcinomas exhibit an activated metabolic and immunosuppressive phenotype with multiple potential therapeutic targets